Skip to main content
Log in

Adipose tissue composition determines its computed tomography radiodensity

  • Computed Tomography
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

Adipose tissue radiodensity in computed tomography (CT) performed before surgeries can predict surgical difficulty. Despite its clinical importance, little is known about what influences radiodensity. This study combines desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and electrospray ionization (ESI) with machine learning to unveil how chemical composition of adipose tissue determines its radiodensity.

Methods

Patients in the study underwent abdominal surgeries. Before surgery, CT radiodensity of fat near operated sites was measured. Fifty-three fat samples were collected and analyzed by DESI-MSI, ESI, and histology, and then sorted by radiodensity, demographic parameters, and adipocyte size. A non-negative matrix factorization (NMF) algorithm was developed to differentiate between high and low radiodensities.

Results

No associations between radiodensity and patient age, gender, weight, height, or fat origin were found. Body mass index showed negative correlation with radiodensity. A substantial difference in chemical composition between adipose tissues of high and low radiodensities was observed. More radiodense tissues exhibited greater abundance of high molecular weight species, such as phospholipids of various types, ceramides, cholesterol esters and diglycerides, and about 70% smaller adipocyte size. Less radiodense tissue showed high abundance of short acyl-tail fatty acids.

Conclusions

This study unveils the connection between abdominal adipose tissue radiodensity and its chemical composition. Because the radiodensity of the fat around the surgical site is associated with surgical difficulty, it is important to understand how adipose tissue composition affects this parameter. We conclude that fat tissue with a higher content of various phospholipids and waxy lipids is more CT radiodense.

Clinical relevance statement

This study establishes the connection between the CT radiodensity of adipose tissue and its chemical composition. Clinicians may use this information for preoperative planning of surgical procedures, potentially modifying their surgical approach (for example, performing partial nephrectomy openly rather than laparoscopically).

Key Points

Adipose tissue radiodensity values in computed tomography images taken prior to the surgery can potentially predict surgery difficulty.

Fifty-three human specimens were analyzed by advanced mass spectrometry, molecular imaging, and machine learning to establish the key features that determine Hounsfield units’ values of adipose tissue.

The findings of this research will enable clinicians to better prepare for surgical procedures and select operative strategies.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

BMI:

Body mass index

CNN:

Convolutional neural networks

CT:

Computed tomography

DESI-MSI:

Desorption electrospray ionization mass spectrometry imaging

ESI:

Electrospray ionization

FWHM:

Full width at half maximum

H&E:

Hematoxylin and eosin

HCD:

Higher energy collisional dissociation

HU:

Hounsfield units

LC-MS:

Liquid chromatography–mass spectrometry

LR:

Linear regression

m/z :

Mass to charge ratio

ML:

Machine learning

MS:

Mass spectrometry

MSE:

Mean square error

NMF:

Non-negative matrix factorization algorithm

Q-TOF:

Quadrupole time-of-flight

SD:

Standard deviation

SIM:

Selected ion monitoring

References

  1. Lamvu G, Zolnoun D, Boggess J, Steege JF (2004) Obesity: physiologic changes and challenges during laparoscopy. Am J Obstet Gynecol 191(2):669–674

    Article  PubMed  Google Scholar 

  2. McIlwaine K, Manwaring J, Ellett L et al (2014) The effect of patient body mass index on surgical difficulty in gynaecological laparoscopy. Aust N Z J Obstet Gynaecol 54(6):564–569

    Article  PubMed  Google Scholar 

  3. Feliciano EMC, Winkels RM, Meyerhardt JA, Prado CM, Afman LA, Caan BJ (2021) Abdominal adipose tissue radiodensity is associated with survival after colorectal cancer. Am J Clin Nutr 114(6):1917–1924

    Article  PubMed  PubMed Central  Google Scholar 

  4. Brown JC, Caan BJ, Meyerhardt JA et al (2018) The deterioration of muscle mass and radiodensity is prognostic of poor survival in stage I-III colorectal cancer: a population-based cohort study (C-SCANS). J Cachexia Sarcopenia Muscle 9(4):664–672

    Article  PubMed  PubMed Central  Google Scholar 

  5. Murphy RA, Register TC, Shively CA et al (2014) Adipose tissue density, a novel biomarker predicting mortality risk in older adults. J Gerontol A Biol Sci Med Sci 69(1):109–117

    Article  CAS  PubMed  Google Scholar 

  6. Shah RV, Allison MA, Lima JA et al (2016) Abdominal fat radiodensity, quantity and cardiometabolic risk: the Multi-Ethnic Study of Atherosclerosis. Nutr Metab Cardiovasc Dis 26(2):114–122

    Article  PubMed  Google Scholar 

  7. Kwon SS, Choi K, Da Nam B et al (2021) Epicardial adipose tissue radiodensity is associated with all-cause mortality in patients undergoing hemodialysis. Sci Rep 11(1):23090

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  8. Tilves C, Zmuda JM, Kuipers AL et al (2020) Associations of thigh and abdominal adipose tissue radiodensity with glucose and insulin in nondiabetic African-ancestry men. Obesity 28(2):404–411

    Article  CAS  PubMed  Google Scholar 

  9. Kim WH, Kim CG, Kim DW (2012) Optimal CT number range for adipose tissue when determining lean body mass in whole-body F-18 FDG PET/CT studies. Nucl Med Mol Imaging 46(4):294–299

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kim YJ, Lee SH, Kim TY, Park JY, Choi SH, Kim KG (2013) Body fat assessment method using CT images with separation mask algorithm. J Digit Imaging 26(2):155–162

    Article  PubMed  Google Scholar 

  11. Din MU, Raiko J, Saari T et al (2017) Human brown fat radiodensity indicates underlying tissue composition and systemic metabolic health. J Clin Endocrinol Metab 102(7):2258–2267

    Article  Google Scholar 

  12. Starekova J, Reeder SB (2020) Liver fat quantification: where do we stand? Abdom Radiol (NY) 45(11):3386–3399

    Article  PubMed  Google Scholar 

  13. Bhullar AS, Anoveros-Barrera A, Dunichand-Hoedl A et al (2020) Lipid is heterogeneously distributed in muscle and associates with low radiodensity in cancer patients. J Cachexia Sarcopenia Muscle 11(3):735–747

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ebadi M, Dunichand-Hoedl AR, Rider E et al (2022) Higher subcutaneous adipose tissue radiodensity is associated with increased mortality in patients with cirrhosis. JHEP Rep 4(7):100495

  15. Wiseman JM, Ifa DR, Song Q, Cooks RG (2006) Tissue imaging at atmospheric pressure using desorption electrospray ionization (DESI) mass spectrometry. Angew Chem Int Ed 45(43):7188–7192

    Article  CAS  Google Scholar 

  16. Margulis K, Chiou AS, Aasi SZ, Tibshirani RJ, Tang JY, Zare RN (2018) Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging. Proc Natl Acad Sci U S A 115(25):6347

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  17. Leuschner J, Schmidt M, Fernsel P, Lachmund D, Boskamp T, Maass P (2018) Supervised non-negative matrix factorization methods for MALDI imaging applications. Bioinformatics 35(11):1940–1947

    Article  PubMed Central  Google Scholar 

  18. Boskamp T, Lachmund D, Oetjen J et al (2017) A new classification method for MALDI imaging mass spectrometry data acquired on formalin-fixed paraffin-embedded tissue samples. Biochim Biophys Acta Proteins Proteom 1865(7):916–926

    Article  CAS  PubMed  Google Scholar 

  19. Nijs M, Smets T, Waelkens E, De Moor B (2021) A mathematical comparison of non-negative matrix factorization related methods with practical implications for the analysis of mass spectrometry imaging data. Rapid Commun Mass Spectrom 35(21):e9181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Keenan MR, Kotula PG (2004) Accounting for Poisson noise in the multivariate analysis of ToF-SIMS spectrum images. Surf Interface Anal 36(3):203–212

    Article  CAS  Google Scholar 

  21. Deepaisarn S, Tar PD, Thacker NA, Seepujak A, McMahon AW (2018) Quantifying biological samples using linear Poisson independent component analysis for MALDI-ToF mass spectra. Bioinformatics 34(6):1001–1008

    Article  CAS  PubMed  Google Scholar 

  22. Piehowski PD, Davey AM, Kurczy ME et al (2009) Time-of-flight secondary ion mass spectrometry imaging of subcellular lipid heterogeneity: Poisson counting and spatial resolution. Anal Chem 81(14):5593–5602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Verbeeck N, Caprioli RM, Van de Plas R (2020) Unsupervised machine learning for exploratory data analysis in imaging mass spectrometry. Mass Spectrom Rev 39(3):245–291

    Article  CAS  PubMed  ADS  Google Scholar 

  24. Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cheng L, Cooks RG (2011) Nondestructive, histologically compatible tissue imaging by desorption electrospray ionization mass spectrometry. Chembiochem 12(14):2129–2132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Baba S, Jacene HA, Engles JM, Honda H, Wahl RL (2010) CT Hounsfield units of brown adipose tissue increase with activation: preclinical and clinical studies. J Nucl Med 51(2):246–250

    Article  PubMed  Google Scholar 

  26. Murano I, Barbatelli G, Parisani V et al (2008) Dead adipocytes, detected as crown-like structures, are prevalent in visceral fat depots of genetically obese mice. J Lipid Res 49(7):1562–1568

    Article  CAS  PubMed  Google Scholar 

  27. Ebadi M, Tandon P, Moctezuma-Velazquez C et al (2018) Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis. J Hepatol 69(3):608–616

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was conducted using the Spatial Metabolomics Unit founded with the help of the Wolfson Foundation and the Wolfson Foundation Charity Trust (award reference PR/oys/jw/md/eh/22747/22641) and the Metabolomics Core Unit, Shared Research Facility, Faculty of Medicine-Hebrew University. This research was supported by Israel Science Foundation (grant number 1840/20), United States–Israel Binational Science Foundation (grant number 2019237), Israel Cancer Research Fund (grant number 20-204-RCDA), Council for Higher Education, Israel (Alon Fellowship), David R. Bloom Center for Pharmaceutical Sciences and The Alex Grass Center for Drug Design and Synthesis.

Funding

The authors state that this work has not received any funding in addition to the grants listed in the Acknowledgements.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katherine Margulis.

Ethics declarations

Guarantor

The scientific guarantor of this publication is O. Gofrit.

Conflict of Interest

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Statistics and Biometry

One of the authors (E. Bentov-Arava) has significant statistical expertise.

No complex statistical methods were necessary for this paper.

Informed Consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical Approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

NA

Methodology

• Prospective

• Observational

• One Institution study

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 558 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zoabi, A., Bentov-Arava, E., Sultan, A. et al. Adipose tissue composition determines its computed tomography radiodensity. Eur Radiol 34, 1635–1644 (2024). https://doi.org/10.1007/s00330-023-09911-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-023-09911-7

Keywords

Navigation